In:
British Journal of Pharmacology, Wiley, Vol. 172, No. 13 ( 2015-07), p. 3341-3352
Kurzfassung:
Hypoxic conditions favour the reduction of nitrite to nitric oxide ( NO ) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 ( ALDH 2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature. Experimental Approach The role of ALDH 2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure ( HF ; 16 patients) in vitro and by measurement of changes in forearm blood flow ( FBF ) during intra‐arterial nitrite infusion (21 patients) in vivo . Specifically, we investigated the effects of (i) ALDH 2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance‐independent inactivation of ALDH 2 by glyceryl trinitrate ( GTN ) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH 2 inhibitors. Key Results Both in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH 2 inhibition, in particular under hypoxia. In humans there was a non‐significant trend towards attenuation of nitrite‐mediated increases in FBF . Conclusions and Implications In human and rat vascular tissue in vitro , hypoxic nitrite‐mediated vasodilatation involves ALDH 2. In patients with HF in vivo , the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms.
Materialart:
Online-Ressource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1111/bph.2015.172.issue-13
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2015
ZDB Id:
2029728-2
SSG:
15,3
